A study found that 18% of HIV positive men acquired hepatitis C virus (HCV) a second time after clearing the virus, with some having third and fourth infections as well, according to findings from the European AIDS Treatment Network presented at the 14th European AIDS Conference this month in Brussels.

Since around 2000 researchers have been reporting outbreaks of apparently sexually transmitted acute hepatitis C among HIV positive men who have sex with men in major cities, first in the U.K. and continental Europe, followed by Australia and the U.S. Factors associated with HCV transmission -- which differ across studies -- include anal intercourse, fisting, group sex, other sexually transmitted infections, and use of non-injected recreational drugs.

Up to one-quarter of people with acute HCV infection clear the virus without treatment, while the remainder develop chronic hepatitis C lasting more than 6 months; spontaneous clearance is less common (around 15%-20%) among people with HIV. Treatment with interferon-based therapy is highly effective during acute infection. However, people who clear HCV naturally or with treatment remain susceptible to reinfection.

Patrick Ingiliz from the Medical Center for Infectious Diseases and fellow investigators with the NEAT Study Group looked at rates of HCV reinfection among HIV positive people in the U.K., Austria, and Germany.

The analysis included 646 men with HIV seen at 6 NEAT centers since 2002 who had acute hepatitis C with either spontaneous clearance (12%) or treatment-induced cure (88%). Men with a second or subsequent HCV infection were included in the analysis. Reinfection was defined as detectable HCV RNA after confirmed spontaneous clearance (negative HCV RNA at 24 weeks after diagnosis) or more than 24 weeks after sustained virological response (SVR) to treatment, or infection with a different genotype or clade than the initial infection.

Most people who did not spontaneously clear their subsequent HCV infection underwent treatment with pegylated interferon plus ribavirin; 2 also received telaprevir (Incivek) and 1 also received simeprevir (an experimental HCV protease inhibitor).

Results

Overall, 113 men (18%) were identified as having at least a second episode of HCV infection, which occurred a median of 162 weeks after he first.

In this group almost all were gay or bisexual men with a median age of 38 years; nearly half had the favorable IL28B CC gene variant.

The most common HCV genotype was 1 (71%), followed by 4 (17%) and 2 (11%); 45% showed a switch of HCV genotypes between their first and second infections.

19 participants had a third episode of HCV infection, occurring a median of 122 weeks after the second diagnosis.

81% were HCV genotype 1 infections, 13% were genotype 4, and 6% were genotype 3; half of these participants had a switch from their previous genotype.

3 people who went to become infected a fourth time, occurring a median of 52 weeks after the third diagnosis.

2 people had HCV genotype 1 and 1 had genotype 4; 67% showed a switch in genotypes.

While 12% of people had spontaneously cleared HCV with treatment following the first infection, 17% experienced spontaneous clearance of the second infection, 47% cleared the third infection, and 33% cleared the fourth infection.

The SVR rate for treatment of the second infection was 45% and 19% were non-responders (about 15% were still being treated or in post-treatment follow-up); cure rates appeared lower during the third and fourth episodes, though numbers were few and some participants were still awaiting SVR data.

CD4 count and use of ART did not predict spontaneous clearance of the second infection.

Second clearers were more likely to have the favorable IL28B gene variant (71% vs 44%) and had lower HCV RNA and higher alanine aminotransferase (ALT), but none of these differences reached statistical significance.

The only significant predictor was clearance of the first infection, which occurred in 32% of second infection clearers and 9% of non-clearers.

Looking at the third episode, spontaneous clearers and non-clearers were equally likely to have the IL28B CC variant (50% each) and HCV RNA was higher among clearers, though not significantly so.

Previous clearers were again more likely to clear their subsequent infection (33% of third infection clearers vs 10% of non-clearers), but this time the difference did not reach significance.

"We confirm high HCV reinfection rates in HIV positive men who have sex with men with one cured episode of HCV," the researchers concluded. "Spontaneous clearance rates seem to increases with reinfection episodes. Spontaneous clearance of a previous episode increases the likelihood to clear again."

"We observed reinfections with the same or with a distinct HCV genotype, and did not find any evidence of immune protection when reinfected with the same genotype," they added.

"Understanding of risk behaviors and promoting strategies for risk-avoidance will be important to prevent reinfections in this population," they recommended.